The immune response in man is regulated by ordered interactions between functionally and phenotypically distinct lymphoid cells (T cells and their subsets, B cells and monocytes) in the context of Ia-like molecules encoded by the HLA complex of genes. Thus, the products of these genes (e.g., DR, DS, SB) control the proliferative response of T cells in mixed lymphocyte reactions, antigen presentation to T cells by macrophages and collaboration between T and B cells. Ten alleles of the HLA-DR locus have been identified and, in addition to influencing allograft survival, alleles of this locus have been associated with susceptibility to a number of diseases including systematic lupus (SLE), rheumatoid arthritis (RA) and multiple sclerosis. We propose to produce a panel of human monoclonal anti-DR (polymorphic) alloantibodies. A human-mouse derived myeloma line, shown to fuse efficiently to human B cells and produce stable human immunoglobulin secreting hybridomas, will be fused to B cells isolated from normal multiparous women and/or transfusion recipients known to contain specific anti-DR antibodies in their sera. The generation of these antibodies will allow a greater understanding of their specificity and functional effects on immune functions of normal and diseased individuals. Ultimately, these antibodies may be useful in the diagnosis and treatment of autoimmune disorders.